The principal objective of the proposal is to develop chemotherapeutic approaches for metastatic tumors based on recently acquired knowledge relating cell surface carbo-hydrates to detachment and implantation of potentially metastatic cells. Inhibitors of sialic acid biosynthesis and its transfer may prevent implantation of metastatic tumors as well as affecting the immunogenicity of the cancer cells. We shall by synthesizing analogues of D-glucosamine, D-mannosamine, NANA, CMP-NANA and D-galactose potentially affecting the anabolic pathways of glycoconjugate biosynthesis. Their effects on hexokinase, CMP-NANA synthetase and CMP-NANA transferase will be determine. All carbohydrate analogs will be tested in metastatic tumors and their effects on immunogenicity will be evaluated. Other test systems have been designed to evaluate their effects on cell surface properties, such as cell surface sialic acid, lectin agglutination and cell social behavior. Combination chemotherapy studies of biologically, active sugar analogs with adriamycin, tunicamycin and local anesthetis are proposed.